Ages at menarche- and menopause-related genetic variants in relation to terminal duct lobular unit involution in normal breast tissue

Hannah Oh, Clara Bodelon, Maya Palakal, Nilanjan Chatterjee, Mark E. Sherman, Laura Linville, Berta M. Geller, Pamela M. Vacek, Donald L. Weaver, Rachael E. Chicoine, Daphne Papathomas, Deesha A. Patel, Jackie Xiang, Susan E. Clare, Daniel W. Visscher, Carolyn Mies, Stephen M. Hewitt, Louise A. Brinton, Anna Maria V. Storniolo, Chunyan HeMontserrat Garcia-Closas, Stephen J. Chanock, Gretchen L. Gierach, Jonine D. Figueroa

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Reduced levels of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini per TDLU, have been associated with higher breast cancer risk. Younger age at menarche and older age at menopause have been previously related to lower levels of TDLU involution. To determine a possible genetic link, we examined whether single-nucleotide polymorphisms (SNPs) previously established in genome-wide association studies (GWAS) for ages at menarche and menopause are associated with TDLU involution. We conducted a pooled analysis of 862 women from two studies. H&E tissue sections were assessed for numbers of TDLUs and acini/TDLU. Poisson regression models were used to estimate associations of 36 menarche- and 21 menopause-SNPs with TDLU counts, acini counts/TDLU, and the product of these two measures, adjusting for age and study site. Fourteen percent of evaluated SNPs (eight SNPs) were associated with TDLU counts at p < 0.05, suggesting an enrichment of associations with TDLU counts. However, only menopause-SNPs had >50 % that were either significantly or nonsignificantly associated with TDLU measures in the directions consistent with their relationships shown in GWAS. Among ten SNPs that were statistically significantly associated with at least one TDLU involution measure (p < 0.05), seven SNPs (rs466639: RXRG; rs2243803: SLC14A2; rs2292573: GAB2; rs6438424: 3q13.32; rs7606918: METAP1D; rs11668344: TMEM150B; rs1635501: EXO1) were associated in the consistent directions. Our data suggest that the loci associated with ages at menarche and menopause may influence TDLU involution, suggesting some shared genetic mechanisms. However, larger studies are needed to confirm the results.

Original languageEnglish
Pages (from-to)341-350
Number of pages10
JournalBreast Cancer Research and Treatment
Volume158
Issue number2
DOIs
Publication statusPublished - 2016 Jul 1
Externally publishedYes

Fingerprint

Menarche
Menopause
Single Nucleotide Polymorphism
Breast
Genome-Wide Association Study
Breast Neoplasms

Keywords

  • Breast histology
  • Lobular involution
  • Menarche
  • Menopause
  • SNP
  • TDLU

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Ages at menarche- and menopause-related genetic variants in relation to terminal duct lobular unit involution in normal breast tissue. / Oh, Hannah; Bodelon, Clara; Palakal, Maya; Chatterjee, Nilanjan; Sherman, Mark E.; Linville, Laura; Geller, Berta M.; Vacek, Pamela M.; Weaver, Donald L.; Chicoine, Rachael E.; Papathomas, Daphne; Patel, Deesha A.; Xiang, Jackie; Clare, Susan E.; Visscher, Daniel W.; Mies, Carolyn; Hewitt, Stephen M.; Brinton, Louise A.; Storniolo, Anna Maria V.; He, Chunyan; Garcia-Closas, Montserrat; Chanock, Stephen J.; Gierach, Gretchen L.; Figueroa, Jonine D.

In: Breast Cancer Research and Treatment, Vol. 158, No. 2, 01.07.2016, p. 341-350.

Research output: Contribution to journalArticle

Oh, H, Bodelon, C, Palakal, M, Chatterjee, N, Sherman, ME, Linville, L, Geller, BM, Vacek, PM, Weaver, DL, Chicoine, RE, Papathomas, D, Patel, DA, Xiang, J, Clare, SE, Visscher, DW, Mies, C, Hewitt, SM, Brinton, LA, Storniolo, AMV, He, C, Garcia-Closas, M, Chanock, SJ, Gierach, GL & Figueroa, JD 2016, 'Ages at menarche- and menopause-related genetic variants in relation to terminal duct lobular unit involution in normal breast tissue', Breast Cancer Research and Treatment, vol. 158, no. 2, pp. 341-350. https://doi.org/10.1007/s10549-016-3859-z
Oh, Hannah ; Bodelon, Clara ; Palakal, Maya ; Chatterjee, Nilanjan ; Sherman, Mark E. ; Linville, Laura ; Geller, Berta M. ; Vacek, Pamela M. ; Weaver, Donald L. ; Chicoine, Rachael E. ; Papathomas, Daphne ; Patel, Deesha A. ; Xiang, Jackie ; Clare, Susan E. ; Visscher, Daniel W. ; Mies, Carolyn ; Hewitt, Stephen M. ; Brinton, Louise A. ; Storniolo, Anna Maria V. ; He, Chunyan ; Garcia-Closas, Montserrat ; Chanock, Stephen J. ; Gierach, Gretchen L. ; Figueroa, Jonine D. / Ages at menarche- and menopause-related genetic variants in relation to terminal duct lobular unit involution in normal breast tissue. In: Breast Cancer Research and Treatment. 2016 ; Vol. 158, No. 2. pp. 341-350.
@article{2e375ae561ad40faa81fbb91621967ed,
title = "Ages at menarche- and menopause-related genetic variants in relation to terminal duct lobular unit involution in normal breast tissue",
abstract = "Reduced levels of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini per TDLU, have been associated with higher breast cancer risk. Younger age at menarche and older age at menopause have been previously related to lower levels of TDLU involution. To determine a possible genetic link, we examined whether single-nucleotide polymorphisms (SNPs) previously established in genome-wide association studies (GWAS) for ages at menarche and menopause are associated with TDLU involution. We conducted a pooled analysis of 862 women from two studies. H&E tissue sections were assessed for numbers of TDLUs and acini/TDLU. Poisson regression models were used to estimate associations of 36 menarche- and 21 menopause-SNPs with TDLU counts, acini counts/TDLU, and the product of these two measures, adjusting for age and study site. Fourteen percent of evaluated SNPs (eight SNPs) were associated with TDLU counts at p < 0.05, suggesting an enrichment of associations with TDLU counts. However, only menopause-SNPs had >50 {\%} that were either significantly or nonsignificantly associated with TDLU measures in the directions consistent with their relationships shown in GWAS. Among ten SNPs that were statistically significantly associated with at least one TDLU involution measure (p < 0.05), seven SNPs (rs466639: RXRG; rs2243803: SLC14A2; rs2292573: GAB2; rs6438424: 3q13.32; rs7606918: METAP1D; rs11668344: TMEM150B; rs1635501: EXO1) were associated in the consistent directions. Our data suggest that the loci associated with ages at menarche and menopause may influence TDLU involution, suggesting some shared genetic mechanisms. However, larger studies are needed to confirm the results.",
keywords = "Breast histology, Lobular involution, Menarche, Menopause, SNP, TDLU",
author = "Hannah Oh and Clara Bodelon and Maya Palakal and Nilanjan Chatterjee and Sherman, {Mark E.} and Laura Linville and Geller, {Berta M.} and Vacek, {Pamela M.} and Weaver, {Donald L.} and Chicoine, {Rachael E.} and Daphne Papathomas and Patel, {Deesha A.} and Jackie Xiang and Clare, {Susan E.} and Visscher, {Daniel W.} and Carolyn Mies and Hewitt, {Stephen M.} and Brinton, {Louise A.} and Storniolo, {Anna Maria V.} and Chunyan He and Montserrat Garcia-Closas and Chanock, {Stephen J.} and Gierach, {Gretchen L.} and Figueroa, {Jonine D.}",
year = "2016",
month = "7",
day = "1",
doi = "10.1007/s10549-016-3859-z",
language = "English",
volume = "158",
pages = "341--350",
journal = "Breast Cancer Research and Treatment",
issn = "0167-6806",
publisher = "Springer New York",
number = "2",

}

TY - JOUR

T1 - Ages at menarche- and menopause-related genetic variants in relation to terminal duct lobular unit involution in normal breast tissue

AU - Oh, Hannah

AU - Bodelon, Clara

AU - Palakal, Maya

AU - Chatterjee, Nilanjan

AU - Sherman, Mark E.

AU - Linville, Laura

AU - Geller, Berta M.

AU - Vacek, Pamela M.

AU - Weaver, Donald L.

AU - Chicoine, Rachael E.

AU - Papathomas, Daphne

AU - Patel, Deesha A.

AU - Xiang, Jackie

AU - Clare, Susan E.

AU - Visscher, Daniel W.

AU - Mies, Carolyn

AU - Hewitt, Stephen M.

AU - Brinton, Louise A.

AU - Storniolo, Anna Maria V.

AU - He, Chunyan

AU - Garcia-Closas, Montserrat

AU - Chanock, Stephen J.

AU - Gierach, Gretchen L.

AU - Figueroa, Jonine D.

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Reduced levels of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini per TDLU, have been associated with higher breast cancer risk. Younger age at menarche and older age at menopause have been previously related to lower levels of TDLU involution. To determine a possible genetic link, we examined whether single-nucleotide polymorphisms (SNPs) previously established in genome-wide association studies (GWAS) for ages at menarche and menopause are associated with TDLU involution. We conducted a pooled analysis of 862 women from two studies. H&E tissue sections were assessed for numbers of TDLUs and acini/TDLU. Poisson regression models were used to estimate associations of 36 menarche- and 21 menopause-SNPs with TDLU counts, acini counts/TDLU, and the product of these two measures, adjusting for age and study site. Fourteen percent of evaluated SNPs (eight SNPs) were associated with TDLU counts at p < 0.05, suggesting an enrichment of associations with TDLU counts. However, only menopause-SNPs had >50 % that were either significantly or nonsignificantly associated with TDLU measures in the directions consistent with their relationships shown in GWAS. Among ten SNPs that were statistically significantly associated with at least one TDLU involution measure (p < 0.05), seven SNPs (rs466639: RXRG; rs2243803: SLC14A2; rs2292573: GAB2; rs6438424: 3q13.32; rs7606918: METAP1D; rs11668344: TMEM150B; rs1635501: EXO1) were associated in the consistent directions. Our data suggest that the loci associated with ages at menarche and menopause may influence TDLU involution, suggesting some shared genetic mechanisms. However, larger studies are needed to confirm the results.

AB - Reduced levels of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini per TDLU, have been associated with higher breast cancer risk. Younger age at menarche and older age at menopause have been previously related to lower levels of TDLU involution. To determine a possible genetic link, we examined whether single-nucleotide polymorphisms (SNPs) previously established in genome-wide association studies (GWAS) for ages at menarche and menopause are associated with TDLU involution. We conducted a pooled analysis of 862 women from two studies. H&E tissue sections were assessed for numbers of TDLUs and acini/TDLU. Poisson regression models were used to estimate associations of 36 menarche- and 21 menopause-SNPs with TDLU counts, acini counts/TDLU, and the product of these two measures, adjusting for age and study site. Fourteen percent of evaluated SNPs (eight SNPs) were associated with TDLU counts at p < 0.05, suggesting an enrichment of associations with TDLU counts. However, only menopause-SNPs had >50 % that were either significantly or nonsignificantly associated with TDLU measures in the directions consistent with their relationships shown in GWAS. Among ten SNPs that were statistically significantly associated with at least one TDLU involution measure (p < 0.05), seven SNPs (rs466639: RXRG; rs2243803: SLC14A2; rs2292573: GAB2; rs6438424: 3q13.32; rs7606918: METAP1D; rs11668344: TMEM150B; rs1635501: EXO1) were associated in the consistent directions. Our data suggest that the loci associated with ages at menarche and menopause may influence TDLU involution, suggesting some shared genetic mechanisms. However, larger studies are needed to confirm the results.

KW - Breast histology

KW - Lobular involution

KW - Menarche

KW - Menopause

KW - SNP

KW - TDLU

UR - http://www.scopus.com/inward/record.url?scp=84976275062&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84976275062&partnerID=8YFLogxK

U2 - 10.1007/s10549-016-3859-z

DO - 10.1007/s10549-016-3859-z

M3 - Article

C2 - 27342457

AN - SCOPUS:84976275062

VL - 158

SP - 341

EP - 350

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

SN - 0167-6806

IS - 2

ER -